JPH0481992B2 - - Google Patents
Info
- Publication number
- JPH0481992B2 JPH0481992B2 JP60003696A JP369685A JPH0481992B2 JP H0481992 B2 JPH0481992 B2 JP H0481992B2 JP 60003696 A JP60003696 A JP 60003696A JP 369685 A JP369685 A JP 369685A JP H0481992 B2 JPH0481992 B2 JP H0481992B2
- Authority
- JP
- Japan
- Prior art keywords
- piperazine
- benzhydryl
- pharmaceutically acceptable
- addition salt
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 239000002253 acid Substances 0.000 claims abstract description 22
- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical class C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 14
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- QXDNXWIWCTWTKE-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]-4-[3-(2,4-dimethoxyphenyl)prop-2-enyl]piperazine Chemical group COC1=CC(OC)=CC=C1C=CCN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 QXDNXWIWCTWTKE-UHFFFAOYSA-N 0.000 claims description 2
- GZKPLVNJJQDIBX-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]-4-[3-(2,3,4-trimethoxyphenyl)prop-2-enyl]piperazine Chemical group COC1=C(OC)C(OC)=CC=C1C=CCN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 GZKPLVNJJQDIBX-UHFFFAOYSA-N 0.000 claims 1
- CFKQPNTZUJFROZ-UHFFFAOYSA-N 1-benzhydryl-4-[3-(2,3,4-trimethoxyphenyl)prop-2-enyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC=C1C=CCN1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 CFKQPNTZUJFROZ-UHFFFAOYSA-N 0.000 claims 1
- JHCKDQZMRGDEFN-UHFFFAOYSA-N 1-benzhydryl-4-[3-(2,4-dimethoxyphenyl)prop-2-enyl]piperazine Chemical compound COC1=CC(OC)=CC=C1C=CCN1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 JHCKDQZMRGDEFN-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 4
- QIRBBJRUUTUFMY-UHFFFAOYSA-N 1-(4-benzhydrylpiperazin-1-yl)-3-phenylprop-2-en-1-one Chemical class C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C(=O)C=CC1=CC=CC=C1 QIRBBJRUUTUFMY-UHFFFAOYSA-N 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 239000013078 crystal Substances 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 20
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000000921 elemental analysis Methods 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- -1 lithium aluminum hydride Chemical compound 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 229940126062 Compound A Drugs 0.000 description 9
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 239000008187 granular material Substances 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 230000017531 blood circulation Effects 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 235000011087 fumaric acid Nutrition 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 229920002261 Corn starch Polymers 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- 229960000876 cinnarizine Drugs 0.000 description 6
- 239000008120 corn starch Substances 0.000 description 6
- 229940099112 cornstarch Drugs 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 5
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- 210000002385 vertebral artery Anatomy 0.000 description 5
- YCYUKHYPIZACDT-OVWKBUNZSA-N 1-benzhydryl-4-[(e)-3-(2,3,4-trimethoxyphenyl)prop-2-enyl]piperazine;hydron;dichloride Chemical compound Cl.Cl.COC1=C(OC)C(OC)=CC=C1\C=C\CN1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 YCYUKHYPIZACDT-OVWKBUNZSA-N 0.000 description 4
- 230000003727 cerebral blood flow Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000001530 fumaric acid Substances 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- LCXSXBYYVYTYDY-WLHGVMLRSA-N (e)-but-2-enedioic acid;piperazine Chemical compound C1CNCCN1.OC(=O)\C=C\C(O)=O LCXSXBYYVYTYDY-WLHGVMLRSA-N 0.000 description 3
- TTXIFFYPVGWLSE-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCNCC1 TTXIFFYPVGWLSE-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 3
- SMANXXCATUTDDT-QPJJXVBHSA-N flunarizine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)N1CCN(C\C=C\C=2C=CC=CC=2)CC1 SMANXXCATUTDDT-QPJJXVBHSA-N 0.000 description 3
- 229960000326 flunarizine Drugs 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- NEFJXFQLIFCPKJ-UHFFFAOYSA-N 1-(4-benzhydrylpiperazin-1-yl)-3-(2,3,4-trimethoxyphenyl)prop-2-en-1-one;hydrochloride Chemical compound Cl.COC1=C(OC)C(OC)=CC=C1C=CC(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 NEFJXFQLIFCPKJ-UHFFFAOYSA-N 0.000 description 2
- OSVPEQXQKPTLND-UHFFFAOYSA-N 1-(4-benzhydrylpiperazin-1-yl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one;hydrochloride Chemical compound Cl.COC1=CC(OC)=CC=C1C=CC(=O)N1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 OSVPEQXQKPTLND-UHFFFAOYSA-N 0.000 description 2
- YBCIUTWWLPREGH-UHFFFAOYSA-N 1-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-3-(2,3,4-trimethoxyphenyl)prop-2-en-1-one;hydrochloride Chemical compound Cl.COC1=C(OC)C(OC)=CC=C1C=CC(=O)N1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 YBCIUTWWLPREGH-UHFFFAOYSA-N 0.000 description 2
- YFAXBPFVXLCKEI-SFKRKKMESA-N 1-[bis(4-fluorophenyl)methyl]-4-[(e)-3-(2,3,4-trimethoxyphenyl)prop-2-enyl]piperazine;dihydrochloride Chemical compound Cl.Cl.COC1=C(OC)C(OC)=CC=C1\C=C\CN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 YFAXBPFVXLCKEI-SFKRKKMESA-N 0.000 description 2
- YQSOIGHEUYMEFI-MWWUGWBXSA-N 1-benzhydryl-4-[(e)-3-(2,4-dimethoxyphenyl)prop-2-enyl]piperazine;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.COC1=CC(OC)=CC=C1\C=C\CN1CCN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 YQSOIGHEUYMEFI-MWWUGWBXSA-N 0.000 description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- ZYOPDNLIHHFGEC-FNORWQNLSA-N Trans-2, 3, 4-Trimethoxycinnamate Chemical compound COC1=CC=C(\C=C\C(O)=O)C(OC)=C1OC ZYOPDNLIHHFGEC-FNORWQNLSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- XSJBIJRHPRQXRO-UHFFFAOYSA-N 1-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-3-(2,4-dimethoxyphenyl)prop-2-en-1-one Chemical compound COC1=CC(OC)=CC=C1C=CC(=O)N1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 XSJBIJRHPRQXRO-UHFFFAOYSA-N 0.000 description 1
- XATDEINGYGBGQZ-AVRNHWNZSA-N 1-[bis(4-fluorophenyl)methyl]-4-[(e)-3-(2,4-dimethoxyphenyl)prop-2-enyl]piperazine;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.COC1=CC(OC)=CC=C1\C=C\CN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 XATDEINGYGBGQZ-AVRNHWNZSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
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- RABWKLPVYFUUIF-WLHGVMLRSA-N OC(=O)\C=C\C(O)=O.COC1=C(OC)C(OC)=CC=C1C=CCN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 Chemical compound OC(=O)\C=C\C(O)=O.COC1=C(OC)C(OC)=CC=C1C=CCN1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 RABWKLPVYFUUIF-WLHGVMLRSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical class O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 201000009939 hypertensive encephalopathy Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Compounds Of Unknown Constitution (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60003696A JPS61161272A (ja) | 1985-01-11 | 1985-01-11 | 新規なピペラジン誘導体および該化合物を有効成分とする医薬組成物 |
| NO855383A NO164170C (no) | 1985-01-11 | 1985-12-30 | Analogifremgangsmaate for fremstilling av terapeutisk aktive 1-benzhydryl-4-cinnamyl-piperazinderivater. |
| US06/815,452 US4703048A (en) | 1985-01-11 | 1985-12-31 | Novel 1-benzhydryl-4-cinnamylpiperazine derivatives, and pharmaceutical compositions comprising said compounds as active ingredient for treating a cerebrovascular disease |
| DE8686100017T DE3678970D1 (de) | 1985-01-11 | 1986-01-02 | Piperazinderivate, verfahren zu ihrer herstellung und diese als wirkstoffe enthaltende pharmazeutische zusammensetzungen. |
| AT86100017T ATE63114T1 (de) | 1985-01-11 | 1986-01-02 | Piperazinderivate, verfahren zu ihrer herstellung und diese als wirkstoffe enthaltende pharmazeutische zusammensetzungen. |
| CA000498854A CA1255313A (en) | 1985-01-11 | 1986-01-02 | Piperazines derivatives, processes for production thereof, and pharmaceutical compositions comprising said compounds as active ingredient |
| EP86100017A EP0187639B1 (de) | 1985-01-11 | 1986-01-02 | Piperazinderivate, Verfahren zu ihrer Herstellung und diese als Wirkstoffe enthaltende pharmazeutische Zusammensetzungen |
| FI860098A FI860098A (fi) | 1985-01-11 | 1986-01-09 | Nya piperazinderivat, foerfarande foer deras framstaellning och farmaceutiska kompositioner som innehaoller dessa foereningar som aktiv ingrediens. |
| GR860045A GR860045B (en) | 1985-01-11 | 1986-01-09 | Novel piperazine derivatives processes for production thereof and pharmaceutical compositions comprising said compounds as active ingredient |
| ES550781A ES8708213A1 (es) | 1985-01-11 | 1986-01-10 | Un procedimiento para preparar un derivado de 1-benzhidril--4-cinamilpiperazina |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60003696A JPS61161272A (ja) | 1985-01-11 | 1985-01-11 | 新規なピペラジン誘導体および該化合物を有効成分とする医薬組成物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61161272A JPS61161272A (ja) | 1986-07-21 |
| JPH0481992B2 true JPH0481992B2 (de) | 1992-12-25 |
Family
ID=11564541
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60003696A Granted JPS61161272A (ja) | 1985-01-11 | 1985-01-11 | 新規なピペラジン誘導体および該化合物を有効成分とする医薬組成物 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4703048A (de) |
| EP (1) | EP0187639B1 (de) |
| JP (1) | JPS61161272A (de) |
| AT (1) | ATE63114T1 (de) |
| CA (1) | CA1255313A (de) |
| DE (1) | DE3678970D1 (de) |
| ES (1) | ES8708213A1 (de) |
| FI (1) | FI860098A (de) |
| GR (1) | GR860045B (de) |
| NO (1) | NO164170C (de) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4792553A (en) * | 1986-02-04 | 1988-12-20 | Terumo Kabushiki Kaisha | Diene derivatives and vasodilators containing the same |
| IT1197348B (it) * | 1986-09-30 | 1988-11-30 | Boehringer Biochemia Srl | Cinnamilammine, processo per la loro preparazione e composizioni farmaceutiche che le contengono |
| FR2614021B1 (fr) * | 1987-04-14 | 1991-03-01 | Andre Buzas | Derives de la 1-((1,1-diphenyl)-1-alcenyl)-piperazine, procede d'obtention et compositions pharmaceutiques les contenant |
| EP3670498A1 (de) * | 2018-12-17 | 2020-06-24 | Gottfried Wilhelm Leibniz Universität Hannover | Verbindungen zur behandlung von hepaci-virusinfektionen und verfahren zur bestimmung der therapie von hepaci-virusinfektionen, insbesondere von hcv-infektionen |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE556791A (de) * | ||||
| GB809760A (en) * | 1956-04-20 | 1959-03-04 | Lab Pharmaceutica Dr C Janssen | Improvements in or relating to pharmacologically active piperazine derivatives and processes for preparing them |
| FR805M (de) * | 1960-06-30 | 1961-09-01 | ||
| FR1303080A (fr) * | 1961-07-25 | 1962-09-07 | Science Union Et Compagnie Soc | Pipérazines disubstituées |
| US3773939A (en) * | 1971-11-24 | 1973-11-20 | Janssen Pharmaceutica Nv | N-arallyl-n'-aralkyl piperazine pharmaceutical compositions |
| JPS5331159B2 (de) * | 1973-08-08 | 1978-08-31 | ||
| JPS606946B2 (ja) * | 1974-03-12 | 1985-02-21 | 東京田辺製薬株式会社 | Ｎ−（３，３−ジフエニルプロピル）−ｎ’−アラルキル置換ピペラジンおよびその塩の製法 |
| DE2502679C3 (de) * | 1975-01-23 | 1981-07-23 | Ludwig Merckle Kg Chem. Pharm. Fabrik, 7902 Blaubeuren | Phenoxyalkancarbonsäurederivate, Verfahren zu ihrer Herstellung und Arzneimittel |
| CH605873A5 (en) * | 1975-12-02 | 1978-10-13 | Chemosynth Ag | Antihistaminic 1-benzhydryl-4-cinnamyl-piperazine prodn. |
| JPS59101475A (ja) * | 1982-12-02 | 1984-06-12 | Nippon Chemiphar Co Ltd | 新規ピペラジン誘導体およびその製造法ならびにこれを含有する脳循環改善剤 |
| IT1213131B (it) * | 1984-02-02 | 1989-12-14 | Yason Srl | Composto ad attivita' calcio antagonista periferica, anticonvulsivante ed eumetabolica cerebrale,metodo per la sua preparazione e composizioni farmaceutiche. |
| JPS60222472A (ja) * | 1984-03-30 | 1985-11-07 | Kanebo Ltd | 新規なピペラジン誘導体および該化合物を有効成分とする医薬組成物 |
-
1985
- 1985-01-11 JP JP60003696A patent/JPS61161272A/ja active Granted
- 1985-12-30 NO NO855383A patent/NO164170C/no unknown
- 1985-12-31 US US06/815,452 patent/US4703048A/en not_active Expired - Fee Related
-
1986
- 1986-01-02 DE DE8686100017T patent/DE3678970D1/de not_active Expired - Fee Related
- 1986-01-02 CA CA000498854A patent/CA1255313A/en not_active Expired
- 1986-01-02 AT AT86100017T patent/ATE63114T1/de not_active IP Right Cessation
- 1986-01-02 EP EP86100017A patent/EP0187639B1/de not_active Expired - Lifetime
- 1986-01-09 GR GR860045A patent/GR860045B/el unknown
- 1986-01-09 FI FI860098A patent/FI860098A/fi not_active Application Discontinuation
- 1986-01-10 ES ES550781A patent/ES8708213A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| US4703048A (en) | 1987-10-27 |
| GR860045B (en) | 1986-05-12 |
| ES8708213A1 (es) | 1987-10-01 |
| NO164170C (no) | 1990-09-05 |
| DE3678970D1 (de) | 1991-06-06 |
| ATE63114T1 (de) | 1991-05-15 |
| NO164170B (no) | 1990-05-28 |
| NO855383L (no) | 1986-07-14 |
| JPS61161272A (ja) | 1986-07-21 |
| ES550781A0 (es) | 1987-10-01 |
| FI860098A0 (fi) | 1986-01-09 |
| CA1255313A (en) | 1989-06-06 |
| FI860098A (fi) | 1986-07-12 |
| EP0187639A1 (de) | 1986-07-16 |
| EP0187639B1 (de) | 1991-05-02 |
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